Dr. Marina-Chiara Garassino, the Thoracic Oncology Unit, Medical
Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori,
Milan, Italy, said: “The results of osimertinib in patients with CNS
metastases are consistent with what has already been reported in the
overall AURA3 population. These data suggest that, like the overall
EGFRm T790M mutation-positive NSCLC population, patients who have
progressed to develop CNS metastases may also be able to benefit from
osimertinib.”

Data were also reported from the BLOOM trial on an EGFRm T790M
mutation-positive NSCLC unselected cohort of 21 patients with
leptomeningeal metastases (LM) treated with osimertinib at an off-label
dose of 160mg po once daily.4 The overall LM response by
investigator assessment was 43%, and of the 10 patients with an
‘abnormal’ neurological assessment at baseline, seven (70%) had an
improvement.4 The most common AEs were diarrhoea (n=13),
nausea (n=11), paronychia (n=9) and rash (n=9). All were Grade 1/2,
except one case each of diarrhoea and nausea (both Grade >3).4
Six patients had dose interruptions, four patients had an AE leading to
dose reduction, and four patients had an AE leading to discontinuation.
Three patients had an AE leading to death, however no deaths were
considered possibly causally-related to osimertinib by the investigator.4

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: “Osimertinib’s potential for
blood-brain barrier penetration was recognised at an early stage of
development, and it is gratifying to see those findings reflected in
positive progression-free survival outcomes in patients with CNS
metastases in the AURA3 trial and in responses in patients with
leptomeningeal metastases in the BLOOM study.”

LM are incurable and notoriously difficult to treat, as existing
therapies are often unable to effectively cross the blood-brain barrier,
leaving patients with limited treatment options.5-7 The use
of osimertinib for these patients is not approved and subject to further
clinical research.

– ENDS –

NOTES TO EDITORS

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death among both men and
women, accounting for about one-quarter of all cancer deaths, more than
breast, prostate and colorectal cancers combined.8 Patients
who have EGFR mutation-positive NSCLC, which occurs in 10-15% of NSCLC
patients in the US and Europe and 30-40% of NSCLC patients in Asia, are
particularly sensitive to treatment with currently available EGFR-TKIs,
which block the cell signalling pathways that drive the growth of tumour
cells.9-12 However, tumours almost always develop resistance
to treatment, leading to disease progression.13 Approximately
half of patients develop resistance to approved EGFR-TKIs such as
gefitinib, erlotinib and afatinib due to the secondary mutation, EGFR
T790M.13,14

About Tagrisso

Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablet has
been approved in 50 countries, including the US, EU, Japan and China,
for patients with EGFR T790M mutation-positive advanced NSCLC.
Eligibility for treatment with osimertinib is dependent on confirmation
that the EGFR T790M mutation is present in the tumour.

Osimertinib is a third generation, irreversible EGFR-TKI designed to
inhibit both EGFR sensitising and EGFR T790M resistance mutations, with
clinical activity against CNS metastases.15 Osimertinib is
also being investigated in the adjuvant and metastatic 1st line
settings, including in patients with and without CNS metastases, in
leptomeningeal metastases, and in combination with other treatments.16-19

About the AURA3 trial

AURA3 compared the efficacy and safety of osimertinib 80mg once daily
and platinum-based doublet chemotherapy in 419 patients with EGFR T790M
mutation-positive, locally advanced or metastatic NSCLC whose disease
had progressed on or after treatment with a previous EGFR-TKI.20
The trial was carried out in more than 130 locations worldwide,
including the US, Canada, Europe, China, Japan, Korea, Taiwan and
Australia.

The primary endpoint of the trial was PFS, and secondary endpoints
included OS, ORR, DoR, DCR, safety and measures of health-related
quality of life (HRQoL).20

About the BLOOM trial

In the BLOOM trial, patients with EGFR mutation-positive advanced NSCLC
who had progressed on prior EGFR-TKI therapy and had leptomeningeal
disease confirmed by positive cerebrospinal fluid cytology received
osimertinib off-label dose 160mg once daily.18 Response was
assessed (by investigator) in two cohorts: EGFR T790M unselected and
EGFR T790M-positive (by central test). Analyses were based on
cerebrospinal fluid (CSF) cytology, brain MRI imaging and neurological
examination every six weeks until progression.18

About Central Nervous System (CNS) Metastases

Parenchymal brain metastases (BM) and leptomeningeal metastases (LM) are
different forms of CNS metastases with a particularly devastating
prognosis.21,22 While separate conditions, they may occur in
parallel and are notoriously difficult to treat. BM are a common
complication of advanced cancer and form when primary tumour cells
disseminate through the blood stream and proliferate in the brain,
whilst LM is much rarer and occurs when tumour cells spread to the
meninges surrounding the brain and spinal cord.20,22,24-26

About AstraZeneca in Lung Cancer

AstraZeneca uses ground-breaking science to develop a wide range of
therapies for patients with lung cancer. We are pioneering
biomarker-guided therapies that aim to eliminate lung cancer by
targeting molecular mutations in tumour cells and by boosting the power
of the immune response against cancer. We are committed to transforming
outcomes for patients with lung cancer, whose treatment options are
currently limited.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly
growing portfolio of new medicines that has the potential to transform
patients’ lives and the Company’s future. With at least six new
medicines to be launched between 2014 and 2020 and a broad pipeline of
small molecules and biologics in development, we are committed to
advance New Oncology as one of AstraZeneca’s five Growth Platforms
focused on lung, ovarian, breast and blood cancers. In addition to our
core capabilities, we actively pursue innovative partnerships and
investments that accelerate the delivery of our strategy, as illustrated
by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalised
combinations, AstraZeneca has the vision to redefine cancer treatment
and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in three
main therapy areas – Oncology, Cardiovascular & Metabolic Diseases and
Respiratory. The Company also is selectively active in the areas of
autoimmunity, neuroscience and infection. AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. For more information, please visit www.astrazeneca.com
and follow us on Twitter @AstraZeneca.

Intended audiences

This press release is issued from AstraZeneca Corporate Headquarters in
Cambridge, UK and is intended to provide information about our global
business. Please be aware that information relating to the approval
status and labels of approved products may vary from country to country,
and a country-specific press release on this topic may have been issued
in the countries where AstraZeneca conducts business.

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